Bone Marrow-derived Cell Therapy for Oral Mucosal Repair after Irradiation
Bone Marrow-derived Cell Therapy for Oral Mucosal Repair after Irradiation
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DOI：
10.1177/0022034514541124
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发表时间：
2014-08-01
影响因子：
7.6
通讯作者：
Asahina, I.
中科院分区：
文献类型：
--
作者：
I, T.;Sumita, Y.;Asahina, I.
口腔粘膜炎（溃疡）是头颈部癌症患者接受放射治疗后的一种严重而痛苦的副作用。然而，目前的临床策略不能有效地预防口腔粘膜炎的发生。在这项研究中，我们调查了骨髓来源的细胞（BMDCs）是否预防放射性口腔粘膜炎的发生和/或降低其严重程度。将新鲜浓缩的雄性C3 H小鼠BMDCs经静脉移植到舌照射后的雌性小鼠体内。照射后14天观察大鼠体重变化及溃疡形成时间。直到溃疡达到最大尺寸（辐射后7天），对收获的舌头进行宏观和组织学分析以检测供体BMDC的行为。照射后2 ~ 5天，移植BMDCs的小鼠表现出更多的干细胞标志物（c-Kit，Sca-1）和EGFR的表达，与未移植的对照小鼠（照射组）相比，凋亡细胞较少。在第7天，在BMDC移植组中观察到更少和更小的溃疡。这些小鼠的舌头保持了上皮厚度，再生活性（血管形成，细胞增殖）高于照射组。标记的BMDC在舌上皮中未检测到，而是在基底细胞层下方的结缔组织（真皮）中检测到。这些发现表明，外源性BMDCs的行为，以减少放射性口腔粘膜炎的旁分泌方式。
Oral mucositis (ulcer) is a serious and painful side effect for patients with head and neck cancer following radiation therapy. However, current clinical strategies cannot efficiently prevent the occurrence of oral mucositis. In this study, we investigated whether bone marrow-derived cells (BMDCs) prevented the occurrence and/or decreased the severity of radiation-induced oral mucositis. Fresh concentrated BMDCs from male C3H mice were transplanted intravenously into female mice after tongue irradiation. For 14 days postirradiation, the changes of body weight and the time courses of ulceration were observed. Until the ulcer reached maximum size (7 days postirradiation), macroscopic and histologic analyses of harvested tongues were performed to detect the behavior of donor BMDCs. Between 2 and 5 days postirradiation, BMDCs-transplanted mice showed more expression of stem cell markers (c-Kit, Sca-1) and EGFR and fewer apoptotic cells when compared with nontransplanted control mice (irradiation group). On day 7, there were fewer and smaller ulcers observed in the BMDCs-transplanted group. Tongues of these mice had preserved their epithelial thickness, and regenerative activities (blood vessels formation, cell proliferation) were higher than they were in the irradiation group. Fluorescently labeled BMDCs were not detected in tongue epithelium but rather in connective tissue (dermis) just below the basal cell layer. These findings suggest that exogenous BMDCs behave to reduce radiogenic oral mucositis in a paracrine manner.